Overview
ATR 1072 is an investigational medicine being studied in adults with PRKAG2 Syndrome. This study will evaluate the safety of ATR 1072 and how the body processes the drug. Researchers will also assess how ATR 1072 affects PRKAG2 activity and measures of heart disease.
Description
ATR 1072 is an antibody-oligonucleotide conjugate (AOC) designed to reduce expression of PRKAG2 through targeted delivery of siRNA to cardiac tissue. This first-in-human, Phase 1/2, open-label, multicenter study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of multiple doses of ATR 1072 in adults with PRKAG2 Syndrome. The study consists of a multiple ascending dose portion (Part A) followed by a dose-expansion cohort at the dose selected in (Part A). After completion of a 48-week treatment period, participants in Parts A and B enter a 42-week extension period followed by a post-treatment follow-up of up to 18 weeks. Approximately 37 participants will be enrolled globally.
Eligibility
Inclusion Criteria:
- Adults 18 to 65 years of age.
- Pathogenic, likely pathogenic, or variant of uncertain significance (VUS) in PRKAG2 confirmed by genetic testing.
- Clinical manifestations consistent with PRKAG2 Syndrome.
- Able and willing to comply with study procedures.
- Able and willing to undergo endomyocardial biopsy procedures (Part A)
Exclusion Criteria:
- Pregnancy or breastfeeding.
- Significant hepatic, renal, hematologic, or cardiovascular abnormalities that may increase study risk.
- NYHA Class IV heart failure or left ventricular ejection fraction \<45%.
- Recent clinically significant cardiovascular events or procedures.
- Prior treatment with prohibited investigational therapies or oligonucleotide therapies within protocol-defined washout periods.
- Any condition that, in the investigator's
